1. Field of the Invention
This invention relates generally to noninvasive measurement of biological parameters using spectroscopy. More particularly, a method and apparatus are disclosed for fluid delivery between an analyzer and a tissue sample to aid in parameter stability during optical sampling.
2. Discussion of the Prior Art
Technical Background
In-vivo measurement of a tissue property or an analyte concentration using optical based analyzers requires that a tissue measurement region be positioned and coupled with respect to an optical interface or probe, such as a tip of a sampling module or tip of a sample probe. The requirements of a sampling interface system for probe placement and coupling depends upon the nature of the tissue properties and analytes under consideration, the optical technology being applied, and the variability of the tissue sample site. Demanding in-vivo applications require a high degree of sampling reproducibility. In one example, a relatively unskilled operator or user must perform the optical measurement. One exemplary application is the noninvasive estimation of glucose concentration through near-infrared spectroscopy in a variety of environments. This problem is further considered through a discussion of the target application and the structure, variability, and dynamic properties of live tissue.
Diabetes
Diabetes is a chronic disease that results in abnormal production and use of insulin, a hormone that facilitates glucose uptake into cells. Diabetics have increased risk in three broad categories: cardiovascular heart disease, retinopathy, and neuropathy. The estimated total cost to the United States economy alone exceeds $90 billion per year. Diabetes Statistics, National Institutes of Health, Publication No. 98-3926, Bethesda, Md. (November 1997). Long-term clinical studies show that the onset of diabetes related complications are significantly reduced through proper control of blood glucose concentrations [The Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Eng J of Med 1993; 329:977-86. A vital element of diabetes management is the self-monitoring of blood glucose concentration by diabetics in the home environment. However, current monitoring techniques discourage regular use due to the inconvenient and painful nature of drawing blood through the skin prior to analysis.
Noninvasive Glucose Concentration Estimation
There exist a number of noninvasive approaches for glucose concentration estimation. These approaches vary widely, but have at least two common steps. First, an apparatus is used to acquire a reading from the body without obtaining a biological sample for every glucose concentration estimation. Second, an algorithm is used to convert the noninvasive reading into a glucose concentration estimation or determination.
Technologies
A number of previously reported technologies for estimating glucose concentration noninvasively exist that involve the measurement of a tissue related variable. One species of noninvasive glucose concentration analyzer uses spectroscopy to acquire a signal or spectrum from the body. Examples include far-infrared absorbance spectroscopy, tissue impedance, Raman, and fluorescence, as well as techniques using light from the ultraviolet through the infrared [ultraviolet (200 to 400 nm), visible (400 to 700 nm), near-infrared (700 to 2500 nm or 14,286 to 4000 cm−1), and mid-infrared (2500 to 14,285 nm or 4000 to 700 cm−1)]. Notably, noninvasive techniques do not have to be based upon spectroscopy. For example, a bioimpedence meter is a noninvasive device. In this document, any device that reads glucose concentration from the body without penetrating the skin or collecting a biological sample with each sample is referred to as a noninvasive glucose concentration analyzer. For the purposes of this document, X-rays and magnetic resonance imagers (MRI's) are not considered to be defined in the realm of noninvasive technologies. It is noted that noninvasive techniques are distinct from invasive techniques in that the sample analyzed is a portion of the human body in-situ, not a biological sample acquired from the human body. The actual tissue volume that is sampled is the portion of irradiated tissue from which light is diffusely reflected, transflected, or diffusely transmitted to the spectrometer detection system.
Instrumentation
A number of spectrometer configurations are reported for collecting noninvasive spectra of regions of the body. Typically a spectrometer has one or more beam paths from a source to a detector. Optional light sources include a blackbody source, a tungsten-halogen source, one or more light emitting diodes, or one or more laser diodes. For multi-wavelength spectrometers a wavelength selection device is optionally used or a series of optical filters are optionally used for wavelength selection. Wavelength selection devices include dispersive elements, such as one or more plane, concave, ruled, or holographic grating.
Sampling
Light is directed to and from a glucose concentration analyzer to a tissue sample site by optical methods, such as through a light pipe, fiber-optics, a lens system, free space optics, and/or a light directing mirror system. Typically, one or more of three modes are used to collect noninvasive scans: transmittance, transflectance, and/or diffuse reflectance. Collected signal is converted to a voltage and sampled through an analog-to-digital converter for analysis on a microprocessor based system and the result displayed.
Human Tissue/Light Interaction
When incident light is directed onto the skin surface, a part of it is reflected while the remaining part penetrates the skin surface. The proportion of reflected light energy is strongly dependent on the angle of incidence. At nearly perpendicular incidence, about four percent of the incident beam is reflected due to the change in refractive index between air (ηD=1.0) and dry stratum corneum (ηD=1.55). For normally incident radiation, this specular reflectance component is as high as seven percent, because the very rigid and irregular surface of the stratum corneum produces off-normal angles of incidence. Regardless of skin color, specular reflectance of a nearly perpendicular beam from normal skin ranges between four and seven percent over the entire spectrum from 250 to 3000 nm. The air-stratum corneum border gives rise to a regular reflection. Results indicate that the indices of refraction of most soft tissue (skin, liver, heart, etc) lie within the 1.38-1.41 range with the exception of adipose tissue, which has a refractive index of approximately 1.46. The 93 to 96 percent of the incident beam that enters the skin is attenuated due to absorption and/or scattering within any of the layers of the skin. These two processes taken together essentially determine the penetration of light into skin, as well as remittance of scattered light from the skin.
Noninvasive Glucose Concentration Determination
There are a number of reports of noninvasive glucose technologies. Some of these relate to general instrumentation configurations required for noninvasive glucose concentration estimation while others refer to sampling technologies. Those related to the present invention are briefly reviewed, infra.
Specular Reflectance
R. Messerschmidt, D. Sting, Blocker device for eliminating specular reflectance from a diffuse reflectance spectrum, U.S. Pat. No. 4,661,706 (Apr. 28, 1987) describe a reduction of specular reflectance by a mechanical device. A blade-like device “skims” the specular light before it impinges on the detector. This system leaves alignment concerns and improvement in efficiency of collecting diffusely reflected light is needed.
R. Messerschmidt, M. Robinson, Diffuse reflectance monitoring apparatus, U.S. Pat. No. 5,636,633 (Jun. 10, 1997) describe a specular control device for diffuse reflectance spectroscopy using a group of reflecting and open sections.
R. Messerschmidt, M. Robinson, Diffuse reflectance monitoring apparatus, U.S. Pat. No. 5,935,062 (Aug. 10, 1999) and R. Messerschmidt, M. Robinson, Diffuse reflectance monitoring apparatus, U.S. Pat. No. 6,230,034 (May 8, 2001) describe a diffuse reflectance control device that discriminates between diffusely reflected light that is reflected from selected depths. This control device additionally acts as a blocker to prevent specularly reflected light from reaching the detector.
S. Malin, G Khalil, Method and apparatus for multi-spectral analysis of organic blood analytes in noninvasive infrared spectroscopy, U.S. Pat. No. 6,040,578 (Mar. 21, 2000) describe the use of specularly-reflected light in regions of high water absorbance, such as 1450 and 1900 nm, to mark the presence of outlier spectra wherein the specularly reflected light is not sufficiently reduced.
K. Hazen, G. Acosta, A. Abul-Haj, R. Abul-Haj, Apparatus and method for reproducibly modifying localized absorption and scattering coefficients at a tissue measurement site during optical sampling, U.S. Pat. No. 6,534,012 (Mar. 18, 2003) describe a mechanical device for applying sufficient and reproducible contact of the apparatus to the sample medium to minimize specular reflectance. Further, the apparatus allows for reproducible applied pressure to the sample site and reproducible temperature at the sample site.
Coupling Fluid
A number of sources describe coupling fluids as a consideration in noninvasive sampling methods and apparatus. Coupling fluids have been long known and understood in the field of optics. Some coupling fluids are used to fill optical irregularities. Others are used for refractive index matching. Some, such as glycerol when used in conjunction with near-infrared light, absorb in the wavelength region of interest. Several reports of optical coupling fluids and a report of a coupling fluid are described, infra.
R. Messerschmidt, Method for non-invasive blood analyte measurement with improved optical interface, U.S. Pat. No. 5,655,530, Aug. 12, 1997 and R. Messerschmidt, Method for non-invasive blood analyte measurement with improved optical interface, U.S. Pat. No. 5,823,951, (Oct. 20, 1998) describe an index-matching medium to improve the interface between a sensor probe and a skin surface during spectrographic analysis. These patents teach an optical coupling medium containing both perfluorocarbons and chlorofluorocarbons that have minimal absorbance in the near-infrared. Since they are known carcinogens, chlorofluorocarbons (CFC's) are unsuitable for use in preparations to be used on living tissue. Furthermore, use of CFC's poses a well-known environmental risk. Additionally, Messerschmidt's interface medium is formulated with substances that are likely to leave artifacts in spectroscopic measurements.
M. Robinson, R. Messerschmidt, Method for non-invasive blood analyte measurement with improved optical interface, U.S. Pat. No. 6,152,876 (Nov. 28, 2000) and M. Rohrscheib, C. Gardner, M. Robinson, Method and apparatus for non-invasive blood analyte measurement with fluid compartment equilibration, U.S. Pat. No. 6,240,306 (May 29, 2001) describe an index-matching optical coupling fluid used to improve the interface between the sensor probe and skin surface during spectroscopic analysis. The index-matching medium is preferably a composition containing chlorofluorocarbons in combination with optionally added perfluorocarbons.
T. Blank, G. Acosta, M. Mattu, S. Monfre, Fiber optic probe guide placement guide, U.S. Pat. No. 6,415,167 (Jul. 2, 2002) describe a coupling fluid of one or more fluorocarbons where a quantity of the coupling fluid is placed at an interface of the tip of an optical probe of a sample module and a measurement site. Advantageously, perfluoro compounds and fluorocarbons lack the toxicity associated with chlorofluorocarbons.
Pressure
E. Chan, B. Sorg, D. Protsenko, M. O'Neil, M. Motamedi, A. Welch, Effects of compression on soft tissue optical properties, IEEE Journal of Selected Topics in Quantum Electronics, Vol. 2, no. 4, 943-950 (1996) describe the effect of pressure on absorption and reduced scattering coefficients from 400 to 1800 nm. Most specimens show an increase in the scattering coefficient with compression.
K. Hazen, G. Acosta, A. Abul-Haj, R. Abul-Haj, Apparatus and method for reproducibly modifying localized absorption and scattering coefficients at a tissue measurement site during optical sampling, U.S. Pat. No. 6,534,012 (Mar. 18, 2003) describe in a first embodiment a noninvasive glucose concentration estimation apparatus for either varying the pressure applied to a sample site or maintaining a constant pressure on a sample site in a controlled and reproducible manner by moving a sample probe along the z-axis perpendicular to the sample site surface. In an additional described embodiment, the arm sample site platform is moved along the z-axis that is perpendicular to the plane defined by the sample surface by raising or lowering the sample holder platform relative to the analyzer probe tip. The '012 patent further teaches proper contact between the probe tip and the sample site to be that point at which specularly-reflected light is substantially zero at the water bands at 1950 and 2500 nm.
M. Makarewicz, M. Mattu, T. Blank, G. Acosta, E. Handy, W. Hay, T. Stippick, B. Richie, Method and apparatus for minimizing spectral interference due to within and between sample variations during in-situ spectral sampling of tissue, U.S. patent application Ser. No. 09/954,856 (filed Sep. 17, 2001) describe a temperature and pressure controlled sample interface. The means of pressure control is a set of supports for the sample that control the natural position of the sample probe relative to the sample.
Data Processing
Several approaches exist that employ diverse preprocessing and post processing methods to remove spectral variation related to the sample and instrument variation: These include: normalization, smoothing, derivatives, multiplicative signal correction, piecewise multiplicative scatter correction, extended multiplicative signal correction, pathlength correction with chemical modeling and optimized scaling, and finite impulse response filtering. A goal of these techniques is to attenuate the noise and instrument variation while maximizing the signal of interest.
Problem
It is desirable to provide a means of assuring that the same tissue sample volume is repeatably sampled, thus minimizing sampling errors due to mechanical tissue distortion, specular reflectance, and probe placement. It would also be highly advantageous to provide a coupling medium to provide a constant interface between an optical probe and the skin at a tissue measurement site that is non-toxic and non-irritating and that doesn't introduce error into spectroscopic measurements. Still further, it would be advantageous to couple a sample probe to skin without inducing spectrally observed stress/strain features.